Complement Pathway

PARI BHARDE

Roll no. 21

Introduction
The complement pathway is an essential part of the innate Classical Pathway Lectin Pathway Alternative Pathway
immune system in microbiology. It consists of a series of
Trigger: Antigen–antibody complexes (IgG or IgM) Trigger: Mannose residues on microbial surfaces Trigger: Pathogen surfaces (e.g., LPS of gram-negative
plasma proteins that work in a cascade to defend against bacteria, fungal walls)
microbial infections, especially bacterial infections. The Steps: Steps:
complement system enhances (or “complements”) the Steps:
1. C1 complex (C1q, C1r, C1s) binds to Fc region of [Link]-binding lectin (MBL) binds
ability of antibodies and phagocytic cells to clear microbes [Link] hydrolysis of C3 → C3(H2O) in plasma.
IgG or IgM (antibody bound to antigen). mannose on bacteria.
and damaged cells. [Link]-associated serine proteases (MASP-1, 2.C3(H2O) binds Factor B, which is cleaved by Factor D →
Minimum 2 IgG or 1 IgM needed.
MASP-2) are activated. Ba + Bb
2. This activates C1r and C1s, which cleave:
[Link] cleave C4 and C2 just like in the 3.C3(H2O)Bb acts as a fluid-phase C3 convertase
C4 → C4a + C4b [Link] microbial surface:
classical pathway.
Biological Functions of C2 → C2a + C2b
[Link]: formation of C3 convertase (C4b2a)
C3b binds Factor B, which is cleaved by Factor D to
3. C4b + C2a form the Classical C3 convertase
Complement Components (C4b2a)
— same as classical.
form C3bBb
Stabilized by Properdin (Factor P)
Pathways 4. C3 convertase cleaves C3 → C3a + C3b
[Link] same downstream steps (C3 → C3a
+ C3b; forms C5 convertase).
Forms Alternative C3 convertase (C3bBb)
C3b-Opsonization – coats pathogens for 5. C3b joins to form C5 convertase (C4b2a3b) 5.C3bBb + C3b = C5 convertase (C3bBb3b)

1. Classical pathway phagocytosis 6. C5 convertase cleaves C5 → C5a + C5b

2. Lectin Pathway C5a, C3a-Anaphylatoxins – trigger
histamine release from mast cells →
3. Alternative Pathway
inflammation
C5a-Chemotaxis – attracts neutrophils,
monocytes
C3d-Helps in B cell activation (part of
adaptive immunity)

Terminal Pathway
Clinical Relevance All three pathways converge at this point

1. C5 convertase cleaves C5 → C5a + C5b

C1, C4, C2-Increased risk of SLE, infections
2. C5b initiates assembly of the Membrane
C3 deficiency-Severe recurrent bacterial infections
Attack Complex (MAC):
C5–C9 deficiency-Increased risk of Neisseria
3. C5b binds C6, C7, C8, and multiple C9s
infections (especially N. meningitidis)
4. Forms C5b-9 MAC → inserts into microbial
C1 esterase inhibitor deficiency-Hereditary
membranes → cell lysis
angioedema
DAF or CD59 deficiency-Paroxysmal nocturnal
hemoglobinuria (PNH)